Funds are requested to purchase a pre-clinical fluorescence molecular tomography (FMT) imaging system to support cancer-related research at the H. Lee Moffitt Cancer Center. This instrument will be housed and operated within the Small Animal Imaging Laboratory, SAIL, situated within the Moffitt vivarium. The Moffitt is the only NIH-designated Comprehensive Cancer Center in the State of Florida, and has recently made a major commitment to developing world class clinical and preclinical cancer imaging capabilities. No other comparable instrument exists in the State of Florida. Thus, this instrument, as all other instruments within SAIL, will be intended to serve as a regional resource. Six major users and 13 minor users have collaborated on this proposal, representing 27 NIH funded grants, including a Program Project in Drug Discovery, a SPORE grant in Thoracic Oncology and a Physical Science Oncology Center grant. These investigators represent five of six research programs within the Cancer Center, including;Drug Discovery, Experimental Therapeutics, Immunology, Molecular Oncology and Risk Assessment, Detection &Intervention. This novel instrumentation will make possible a number of currently inaccessible studies in four distinct areas of research: therapy response assessment, molecular profiling, cell tracking in immunotherapy, and antibody/ligand/nanoagent biodistribution. For therapy response assessment, tumor expression of fluorescent protein expression and the bioactivity of a number of commercially available fluorescent probes can be used to monitor response to experimental drugs and therapeutic regimens. For molecular profiling, novel and available targeted fluorescent probes may be used to identify the expression of key diagnostic and prognostic markers. Cell tracking can be monitored by adoptive transfer of cells engineered to express fluorescent protein into congenic mouse strains and imaging co-localization to fluorescent protein expressing xenograft tumors using multiple channels. Finally, binding specificity, biodistribution and pharmacokinetics of uptake and clearance can be quantitatively assessed for novel targeted molecular imaging agents under development. Public Health Relevance: Funds are requested to purchase a pre-clinical animal imaging instrument for the H. Lee Moffitt Cancer Center, the only NCI designated Comprehensive Cancer Center in the State of Florida. This fluorescence molecular tomography instrument is capable of generating quantitative measurements and high-resolution tomographic images of internally expressed fluorescent proteins, and fluorescent probes associated with internal organs, orthotopic tumor models and biochemical activities. Such an instrument will enable investigators to monitor therapy response, profile molecular phenotypes of cancers, noninvasively track cells during immunotherapy and track the distribution of fluorochrome-conjugated molecules throughout the body. Since this capability is not currently available in the State of Florida, this instrument will serve as a regional resource for investigators at other institutions as well.